Recent information suggests that human marrow aplasias may have immunopathologic basis and that suppression and neoplastic transformation of the immunologic and hemopoietic systems share a common etiology and pathogenesis. Inherent limitations to the study of human aplastic anemias and preleukemic syndromes are their obscure etiology, heterogeneous nature, difficulty of prospective studies, and complicating effects of treatment. Aplastic anemia also is a naturally occurring disease in cats. Feline aplastic anemia also has preleukemic significance, is associated with immunosuppression, and can be reproduced experimentally by inoculation of cats with feline leukemia virus (FeLV). The hematologic features of the feline disase are characterized and immunofluorescence techniques are available to detect intracellular FeLV antigens, a transformation-related cell membrane neoantigen (the feline oncornavirus-associated cell membrane antigen-FOCMA), and the host immunologic response to these antigens. The objective of this proposal is to employ the feline anemia model to investigate the mechanisms of acquired bone marrow aplasias and to develop and evaluate therapeutic regimes for aplastic anemias. In order to compare the pathogenesis of vial vs chemically induced chronic marrow suppression, a model of benzene-induced nonregenerative anemia in cats also has been developed. The specific aims of this study are: (1) to culture and characterize the erythropoietic (CFU-E) and myelopoietic (CFU-C) marrow progenitor cells in normal cats and cats with aplastic anemia induced by FeLV or benzene, (2) to correlate marrow erythroid and myeloid cell growth and differentiation with the presence of FeLV antigens and FOCMA, (3) to determine whether humoral factors, lymphoid cells, or leukemia virus-associated proteins mediate marrow suppression in vitro and in vivo, (4) to characterize hemo-suppressive factors and/or cells and determine their relationship to the immunosuppression in preleukemic and anemic cats, and (5) to develop methods to treat aplastic anemia by eliminating suppressors and infusing autologous cryopreserved pre-disease marrow cells or marrow cells "cured" of aplasia in vitro.